Patient navigation can be a means to positively influence oncology clinical trial participation. With a navigation focus on minority and underserved populations, this care concept promotes a trusting relationship among the research staff and the patient population served. An overview of clinical trials is described followed by a historical perspective of clinical trials, and current mandates are reviewed. A background of known barriers to clinical trial participation is disclosed since this is a common focal point of the navigation development in disparate communities. With respect to the individuality of a healthcare system’s focus on increasing oncology clinical trial participation, different avenues of navigation are explored to promote success on this objective. A common foundation for each avenue to increase clinical trial participation is built on the trusting relationship that the navigator establishes with each patient. The logistics of navigation training with standardized metrics that can apply to any navigation program engaged in clinical trial promotion is described. Patient navigation can be employed as a reasonable way to increase oncology clinical trial participation and trial retention.